The invention relates to the use of non-NMDA antagonists or their physiological salts for the production of pharmaceutical agents for treatment of withdrawal symptoms after drug abuse as well as the combination of the pharmaceutical agents with NMDA antagonists.
Both in clinical studies and in practice, frequently long-term treatments with benzodiazepine-receptor-binding pharmaceutical agents, such as, e.g., diazepam (valium), are performed in spasmodic conditions and sleep disturbances or for sedation and reducing anxiety. The greatest problem for the patients are the withdrawal symptoms occurring after discontinuing these substances. Symptoms include muscular stiffness, tremor, seizures and anxiety conditions. These withdrawal symptoms also occur after intake of drugs or substances with abuse potential, especially after discontinuing the treatment with pharmaceutical agents which cause an addiction, such as, for example, benzodiazepines, opiates, hallucinogens, barbiturates, after use of other narcotics such as cocaine or heroin, or after the use of alcohol. As substances which can cause a physical and psychological dependence, the following can be mentioned as examples:
1. Opiates such as morphine and its derivatives, as well as substances with a morphine effect such as methadone, pethidine and meperidine as well as codeine and heroin;
2. Hallucinogens such as fentanyl, .alpha.-methylfentanyl, 3-methylfentanyl, etryptamine, dimethyltryptamine and amphetamines, for example, amphetamine, methamphetamine, phenmetrazine, methylphenidate and dexamphetamine;
3. Compounds with sedative effects, such as benzodiazepines, for example, diazepam and chlordiazepoxide, meprobamate and barbiturates, for example, hexobarbital, phenobarbital and heptabarbital;
4. Alcohols such as ethanol, and
5. Alkaloids, such as cocaine.
The role of excitatory amino acids in the central nervous system has gained increasing interest in recent years. Glutamate thus was identified as a neurotransmitter and three other receptor subtypes for excitatory amino acids were found and characterized, which were named after the specifically effective glutamate-analogous amino acids N-methyl-D-aspartate (NMDA), kainate and quisqualate receptors.
The benzodiazepines are psychopharmaceutical agents for which it is best known that the long-term treatment, as has been proved, to lead to tolerance and dependence. A sudden interruption in the intake can result in undesirable withdrawal symptoms such as seizures, muscular stiffness and anxiety conditions, whose mechanisms until now have been largely unclarified since sensitive methods for the objective description of the withdrawal symptoms are lacking in animal experiments.
Withdrawal is considered as a time-dependent but homogeneous clinical and pathophysiological process whose symptoms are attributable to the presence of a gamma-aminobutyrate-BDZ/Cl of an ionophoric receptor-effector complex.